The Agricultural Health Study (AHS) is a long-term prospective study of potential health effects associated with exposure to pesticides and other agricultural exposures. The study is a collaboration of the National Cancer Institute, the National Institute of Environmental Health Sciences, and the US Environmental Protection Agency. Farmers and their spouses and children are exposed to numerous potential hazards - many of which, such as pesticides, are relevant to the population at large. Farmers have been shown to be at increased risk for some cancers. Experimental and human studies of acute or high-dose exposures suggest that farmers may also be at increased risk of other adverse health effects. We are examining cancer incidence and other health endpoints in a prospective study of licensed pesticide applicators, spouses and children from North Carolina (NC) and Iowa (IA). Over a 3-year period, we enrolled more than 57,000 licensed applicators, representing 82% of eligible private pesticide applicators (largely farmers) in IA and NC and 43% of commercial applicators from Iowa. About 40% of the private applicators also completed a more detailed take-home questionnaire covering farming practices and health. Nearly 32,000 spouses of farmer applicators enrolled and 2/3 of these also provided data on reproductive health, including information on all children under age 21. [unreadable] [unreadable] Cancer incidence among the applicators, spouses, and children is determined through linkage with the population-based cancer registries in IA and NC. Follow-up computer-assisted telephone interviews are used to update exposure information and to collect information on changes in health status since enrollment in the study. Buccal-cell samples are being collected from participants in order to extract DNA for future analyses of gene and environment interactions. In addition, a dietary assessment (food frequency questionnaire) is self-completed and returned by mail. In-depth assessment of agricultural exposures is being made for a small sample of farmers and their families in order to validate the questionnaires and facilitate exposure classification. Both environmental and biological samples are being collected. Non-cancer outcomes of particular interest in this follow-up period include Parkinson's Disease, neurological symptoms related to pesticide use, autoimmune diseases, gestational diagetes, and premature ovarian failure in addition to cancer. [unreadable] [unreadable] [unreadable] Recent results from the Agricultural Health Study include: 1) Long-term exposure to pesticides is associated with increased reporting of neurological symptoms typically seen following acute exposures; 2) Increased risk for accident mortality among farm children; 3) Decreased fertility associated with parental use of solvents and obesity in men; 4) A consistent and strong association between organophosphate pesticides as well as the herbicide chlorimuron-ethyl and wheeze among commercial pesticide applicators; 5) A link between pesticide use and self-reported Parkinson's disease; 6) The absence of an association between pesticides and farm factors and risk for rheumatoid arthritis; 7) A link between specific hormonally active pesticides and late age at menopause; and 8) A link between personal use of agricultural pesticides in early pregnancy and risk for gestational diabetes among spouses of pesticide applicators.[unreadable] [unreadable] We continue to analyze cross-sesctional data on farm exposures and specific respiratory diseases, including farmers lung and chronic bronchitis. Other work focuses on preeclampsia and use of pesticides during pregnancy as well as other adverse pregnancy and birth outcomes. We are collaborating with investigators from the University of Iowa on a study of neurobehavioral function in a subset of the cohort. A pilot study of the feasibility of using hormonal assays to assess puberty onset and to study the potential link between pesticides and puberty onset is being carried out. Phase III follow-up telephone interviews are being conducted. Respiratory disease incidence will be a major focus of our efforts in the next few years.